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Co-occurrence of two cases of progressive multifocal leukoencephalopathy in a natalizumab "infusion group"

J Havla1, A Berthele, T Kümpfel

  • 1Institute of Clinical Neuroimmunology, Ludwig-Maximilians-University, Germany.

Multiple Sclerosis (Houndmills, Basingstoke, England)
|November 6, 2012
PubMed

Insights

Two cases of progressive multifocal leukoencephalopathy (PML) occurred in the same natalizumab (NAT) infusion group. Unique JC virus (JCV) DNA sequences in patients argue against transmission, suggesting co-occurrence is statistically probable.

Area of Science:

  • Neuroimmunology
  • Viral Pathogenesis
  • Clinical Neurology

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a rare, severe demyelinating disease of the central nervous system.
  • JC virus (JCV) is the causative agent of PML, typically reactivating in immunocompromised individuals.
  • Natalizumab (NAT) is a monoclonal antibody used for treating relapsing-remitting multiple sclerosis (RRMS), associated with an increased risk of PML.

Observation:

  • Two patients within the same natalizumab infusion group developed PML concurrently.
  • The patients had received natalizumab for over four years at the same medical facility.
  • This observation raised initial concerns regarding potential viral transmission within the infusion group.

Findings:

  • Analysis of JC virus (JCV) DNA from cerebrospinal fluid (CSF) revealed distinct non-coding control region (NCCR) sequences in both PML patients.
  • The unique NCCR sequences differed from the JCV archetype and from each other.
  • These genetic differences strongly argue against direct viral transmission between the two patients.

Implications:

  • The concurrent occurrence of PML in the same NAT infusion group was likely coincidental, not due to transmission.
  • Statistical analysis suggests that such co-occurrences, while rare, are predictable.
  • This highlights the importance of continued vigilance and understanding of PML epidemiology in patients treated with natalizumab.
Keywords:
JC virusNatalizumabPMLmultiple sclerosisprogressive multifocal leukoencephalopathy

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